	US 7,544,676 B2
	Sulfamoyl benzamides and methods of their use
Roland E. Dolle, King of Prussia, Pa. (US); and Karin Worm, East Windsor, N.J. (US)
Assigned to Adolor Corporation, Exton, Pa. (US)
Filed on Nov. 09, 2006, as Appl. No. 11/558,332.
Claims priority of provisional application 60/735571, filed on Nov. 10, 2005.
Prior Publication US 2008/0058302 A1, Mar. 06, 2008
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/195 (2006.01); A61K 31/34 (2006.01); A61K 31/397 (2006.01); A61K 31/40 (2006.01); A61K 31/445 (2006.01); A61K 31/535 (2006.01); A61P 25/00 (2006.01); C07C 307/02 (2006.01); C07D 265/30 (2006.01)

U.S. Cl. 514—210.01 [514/563; 514/238.8; 514/237.8; 514/323; 514/424; 514/470; 544/144; 544/158; 546/201; 548/484; 548/542; 548/950]

74 Claims

1. A compound of formula I:

wherein:

R¹is NR^yR^z;

each R^x, R^yand R^zis independently H, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroaralkyl; or R^yand R^z, when taken together with the nitrogen atom to which they are attached, form a 3- to 8-membered heterocycloalkyl ring in which 1 or 2 of the heterocycloalkyl ring carbon atoms independently may each be optionally replaced by —O—, —S—, —N(R⁹)—, —N(R¹⁰)—C(═O)—, or —C(═O)—N(R¹⁰)—;

R²and R³are each independently H, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroaralkyl, provided that at least one of R²and R³is other than H; or R²and R³, when taken together with the nitrogen atom to which they are attached, form a 3- to 8-membered heterocycloalkyl ring in which 1 or 2 of the heterocycloalkyl ring carbon atoms independently may each be optionally replaced by —O—, —S—, —N(R⁹)—, —N(R¹⁰)—C(═O)—, or —C(═O)—N(R¹⁰)—;

R⁴is H or alkyl;

R⁵is:

Z is

a 1 or 2 heteroatom containing heteroaryl, or a 1 or 2 heteroatom containing heterocycloalkyl, wherein each heteroatom of said heteroaryl or heterocycloalkyl group is independently selected from the group consisting of N, N(R¹¹), O, and S;

each R^aand R^bis independently H or alkyl;

R^cis H, alkyl, or aryl;

R^dand R^eare each independently H or alkyl, with the proviso that at least two of R^c, R^d, and R^eare other than H; or R^dand R^e, taken together with the carbon atom to which they are attached, form a carbocyclic or heterocyclic ring; or R^c, R^d, and R^e, taken together with the carbon atom to which they are attached, form a bicycloalkyl, tricycloalkyl, heterobicyclic, or heterotricyclic ring;

R⁶and R⁸are each independently H or alkyl;

each R⁹is independently H, alkyl, aryl, —C(═O)—R¹¹, —C(═O)—OR¹¹, —[C(R¹¹)(R¹¹)]_s—C(═O)—OR¹¹, —SO₂R¹¹, or —C(═O)N(R¹¹)R¹¹;

each R¹⁰is independently H, alkyl, or aryl;

each R¹¹is independently H or alkyl;

r is 0, 1, 2, or 3; and

s is 1, 2, 3, or 4;

with the provisos that:

(1) when R^dand R^eare each independently H or alkyl, then R^cis H or alkyl;

(2) when R^cis aryl, then R^dand R^e, taken together with the carbon atom to which they are attached, form a carbocyclic or heterocyclic ring;

(3) NR^yR^zis other than an optionally substituted piperazine ring; and

(4) when R⁴is H, R⁵is sec-butyl, and R⁶, R⁸, and one of R²and R³is H, then the other of R²and R³is other than;

or a pharmaceutically acceptable salt thereof.